Sustained Increase in the Oral Bioavailability of Loperamide after a Single Oral Dose of HM30181, a P-glycoprotein Inhibitor, in Healthy Male Participants.

HM30181 is a new P-glycoprotein (P-gp) inhibitor. This study was conducted to investigate the effect of HM30181 and its duration of action on P-gp inhibition using loperamide as a probe drug. An open-label, five-period, fixed-sequence, cross-over study was conducted in 25 healthy Korean participants, who received a single oral dose of loperamide at 16 mg in five periods lasting for 17 days. In period II, participants also randomly received a single oral dose of HM30181 at 1, 5, 10, 15 mg simultaneously with loperamide. Serial pharmacokinetic blood samples were obtained up to 72 and 336 hr after loperamide and HM30181 administration, respectively. A mixed-effects analysis was performed to compare the area under the plasma concentration versus time curve from time 0 to 72 hr (AUC0-72 hr ) between periods and HM30181 dose groups. Tolerability was also assessed. The AUC0-72 hr of repeatedly administered loperamide was significantly increased 1.18-1.62 times for up to 14 days after a single oral administration of HM30181, particularly at doses ≥10 mg although the between-group difference failed to reach statistical significance. Plasma HM30181 was not detected in many participants including none at any sampling points beyond 48 hr after administration. Most adverse events (AEs) were mild to moderate and resolved spontaneously. The oral bioavailability of loperamide was significantly enhanced by a single oral administration of HM30181, which was sustained for up to 14 days. HM30181 was well tolerated in this selected population.

Factors promoting the prolonged shedding of the pandemic (H1N1) 2009 influenza virus in patients treated with oseltamivir for 5 days.

BACKGROUND: The duration of viral shedding is an important determinant of infectivity and transmissibility and provides vital information for effective infection prevention and control. However, few studies have evaluated viral shedding in patients admitted to hospital with 2009 H1N1 influenza and treated with oseltamivir. OBJECTIVE: To determine the incidence of prolonged 2009 H1N1 influenza viral shedding in patients treated for 5 days with oseltamivir and to identify factors that promote prolonged viral shedding. METHODS: This was a prospective, observational cohort study of 173 patients infected with 2009 H1N1 influenza (confirmed by RT-PCR) who were admitted to isolation rooms in the emergency department of our hospital between August 25, 2009 and December 31, 2009. All of the patients were treated according to institutional protocols and received routine follow-up RT-PCR testing after 5 days of oseltamivir therapy. Prolonged viral shedding was defined as a positive follow-up RT-PCR result. RESULT: Of the 173 patients in our cohort, 88 (50.8%) showed persistent viral shedding after oseltamivir treatment. Viral shedding was significantly prolonged if antiviral therapy was started ≥ 2 days after symptom onset (OR 2.74, 95% CI 1.29-5.82), if there were major comorbidities (OR 3.07, 95% CI 1.29-7.32), and/or if respiratory symptoms were still present on the day 5 of antiviral treatment (OR 4.13, 95% CI 2.10-8.11). CONCLUSIONS: The presence of major comorbidities, a delay in initiating antiviral treatment, and continuing respiratory symptoms after 5 days of antiviral treatment are associated with prolonged shedding of the 2009 H1N1 influenza virus.